JAC-Antimicrobial Resistance最新文献

Objectives: In this multicentre, prospective study, we aimed to describe the use of isavuconazole in critically ill adult patients in ICU, in terms of patient characteristics, infection characteristics and outcomes.

Methods: Prospective, observational study of ICU patients treated with isavuconazole from January 2023 to 30 April 2025 in 17 centres (ISA-SITA study within the MULTI-SITA project).

Results: A total of 177 ICU patients treated with isavuconazole were included in the study. Most patients showed at least one European Organisation for Research and Treatment of Cancer/Mycoses Study Group Education and Research Consortium (EORTC/MSGERC) or FUNgal Diseases in adult patients in Intensive Care Unit (FUNDICU) host factor (141/177, 79.7%). Overall, 82/177 patients (46.3%) had either proven or probable invasive mould disease (6 and 76, respectively, mostly invasive pulmonary aspergillosis). In patients with proven or probable disease, 30-day mortality was 44.0%, and 90-day mortality was 62.2%. In multivariable analyses, SOFA score (HR 1.14 per one point increase, 95% CI 1.03-1.26, P = 0.010) and concomitant bacterial pneumonia (HR 2.32, 95% CI 1.17-4.59, P = 0.016) were associated with 30-day mortality, whereas prior hospitalization (HR 2.26, 95% CI 1.19-4.27, P = 0.013) and SOFA score (HR 1.17 per one point increase, 95% CI 1.07-1.28, P < 0.001) were associated with 90-day mortality.

Conclusions: Diverse patterns of isavuconazole use were observed in a large cohort of critically ill adult patients, and the drug was well tolerated. Mortality was lower than many previous estimates in critically ill patients and could serve as a basis for future standardized comparisons.

Background: The hospital environment is a proven hotspot for antimicrobial-resistant bacteria, which may be released through hospital wastewater into the environment and municipal wastewater. The aim of this study was to monitor the occurrence of and perform molecular characterization of MDR ESBL Enterobacterales isolated from Parirenyatwa Hospital wastewater, Harare, Zimbabwe.

Methods: This was a cross-sectional study. Enterobacterales from sixty-four 500 mL samples of hospital wastewater from three drainage sites of Parirenyatwa Hospital were isolated. A modified double disc synergy test was used to confirm ESBL Enterobacterales before genotyping with multiplex PCR.

Results: The majority of isolates came from the main hospital drainage site. All the isolated Enterobacterales showed MDR. Of the 33 Enterobacterales isolated from hospital wastewater, 8 (24%) were ESBL-producing: 5/8 (63%) Escherichia coli, 2/8 (25%) Klebsiella pneumoniae, and 1/8 (12%) Citrobacter freundii. The multiple antibiotic resistance index (MARI) obtained from the ESBL-producing Enterobacterales isolates ranged from 0.5 to 0.75. Seven (87.5%) isolates harboured the bla _CTX-M gene and five (62.5%) isolates had the bla _TEM gene, with four (50%) isolates containing both genes. Three isolates contained the bla _CTX-M gene only and one contained only bla _TEM. The bla _SHV gene was not detected.

Conclusions: MDR ESBL-producing Enterobacterales were identified from Parirenyatwa Hospital wastewater. The MARI greater than 0.2 indicated that these isolates were from a high-risk source of contamination.

[This corrects the article DOI: 10.1093/jacamr/dlaf103.].

Background: Pneumocystis pneumonia (PCP) is an opportunistic fungal infection. Several guidelines have been published to support its clinical management. However, the complexity and breadth of these guidelines pose challenges for consistent implementation in routine clinical practice.

Objectives: To develop a scoring tool and quality indicator that facilitates clinical decision making and quantifies adherence to best-practice guidelines for PCP in patients with and without HIV.

Methods: Key recommendations for the diagnosis, treatment and follow-up of PCP were extracted from current guidelines of the European Council on Infections in Leukaemia (ECIL), the American Society of Transplantation Infectious Diseases Community of Practice (AST-IDCOP), and the IDSA guidelines. Each recommendation was assigned a point value ranging from -1 to 3, weighted according to the strength of recommendation and level of evidence.

Results: The proposed 2025 European Confederation of Medical Mycology (ECMM) QUALity (EQUAL) Pneumocystis Score consists of 24 items for patients with HIV and 22 for patients without HIV. For diagnosis, bronchoalveolar lavage and immunofluorescence assays received the highest scores due to their superior sensitivity and specificity for sampling and analysis. Trimethoprim/sulfamethoxazole is the treatment of choice and was awarded with the highest score. The addition of corticosteroids for patients with HIV and respiratory failure completes the treatment category. The score is completed with the patient follow-up. For HIV patients a maximum score of 31 and for non-HIV patients a maximum score of 27 is achievable.

Conclusions: The 2025 EQUAL Pneumocystis Score offers a concise, evidence-based tool for the optimal management of PCP. This can be useful in daily practice for a quick overview and may be used to measure guideline adherence in research settings. It has not yet been assessed whether higher EQUAL Pneumocystis Scores are associated with improved patient outcomes.

Objectives: To evaluate the environmental impact of prolonged IV antimicrobial courses and identify opportunities for improved antimicrobial stewardship (AMS) practices.

Methods: A retrospective cross-sectional study was conducted using AMS ward-round data from January 2023 to December 2024 at a tertiary hospital in Dublin, Ireland. Data on IV antimicrobial prescriptions, AMS recommendations for discontinuation or IV to oral switch (IVOS) and prescriber acceptance were reviewed. A life cycle assessment, informed by published literature, was used to estimate the carbon footprint associated with IV use.

Results: Of 1929 antimicrobial prescriptions reviewed, 58% (n = 1119) were being administered IV. Among 435 IV prescriptions with AMS, recommendations to stop (n = 357) or IVOS (n = 78), 229 (52.6%) were accepted, resulting in a reduction of 106.5 kg of clinical waste and 261.2 kg carbon dioxide equivalents (CO₂e) emissions. The remaining 206 IV prescriptions (47.4%) were categorized as prolonged IV prescriptions, generating 98.8 kg of clinical waste and 245.8 kg CO₂e; averaging 0.48 kg of waste and 1.19 kg CO₂e per prescription. To contextualize, the carbon footprint of each prolonged prescription equates to driving 6.2 km, performing 10 chest X-rays or operating a 10 W light-emitting diode bulb continuously for 1200 h. Piperacillin-tazobactam, amoxicillin-clavulanic acid, cefuroxime, metronidazole and meropenem together accounted for over 84% of total emissions, with piperacillin-tazobactam alone contributing 97.5 kg CO₂e and 41.6 kg of waste from 62 prolonged prescriptions.

Conclusions: In addition to patient safety risks, prolonged IV antimicrobial courses generate considerable environmental waste. Aligning AMS with sustainability goals may contribute to addressing the dual crises of antimicrobial resistance and climate change.

Objectives: Evaluation of differences in the intestinal microbiome and resistome among high-risk patients (i.e. intensive care, oncology, transplant recipients) who are and are not colonized with carbapenem-resistant Enterobacterales (CRE).

Methods: One hundred and twelve rectal swabs were obtained from 85 patients with known CRE colonization status and cohorted. Long-read metagenomic next-generation sequencing (mNGS) was performed on rectal swabs. Microbiome and resistome analysis were performed by assessing α-diversity, β-diversity, relative abundance assessment and linear discriminant analysis effect size (LEfSe), comparing patients colonized (CRE positive) and not colonized (CRE negative) with CRE. Longitudinal analysis of sequential swabs collected over multiple hospital encounters on a subset of patients was performed at the patient level.

Results: The microbiomes of cohorts were similar when comparing α- and β-diversity measures and relative abundance. LEfSe analysis identified Gram-negative pathobionts enriched among CRE-positive samples and Gram-positive taxa enriched among CRE-negative samples. α-Diversity of the resistome differed at class, gene and allele levels. Relative abundance and LEfSe analysis demonstrated enrichment of genes conferring β-lactam resistance among CRE-positive patients; LEfSe also demonstrated enrichment of antimicrobial resistance genes to multiple antimicrobial classes. At the patient level, fluctuations in the microbiome and resistome among longitudinally collected swabs were associated with antibiotic exposure.

Conclusions: Differences between the microbiomes of CRE-positive- and CRE-negative-colonized patients at the cohort level were relatively muted, whereas statistically significant differences were observed among their resistomes. In patients followed longitudinally, shifts in microbiome and resistome composition were dramatic in between encounters and antibiotic exposures.

Objective: Guidelines recommend redosing with intravenous prophylactic antibiotics when excessive bleeding exceeds 1500 mL during surgery based on the pharmacokinetics data of cefazolin. However, the necessity for redosing of other antibiotics and the threshold volume of blood loss necessitating such supplementation remain undefined. We investigated plasma antibiotic concentrations during liver transplant surgery in patients with frequent excessive bleeding.

Methods: A single-centre, prospective, observational pharmacokinetic study was conducted. Adult liver transplant recipients who received 2 g of ampicillin and 1 g of sulbactam every 3 h during surgery were included. Blood samples were collected hourly during surgery, and intraoperative bleeding amounts were reviewed from anaesthesia records. Plasma concentrations of ampicillin and sulbactam were determined using validated liquid chromatography-tandem mass spectrometry. The probability of target attainment was set at 80% free time above the MIC (fT > MIC).

Results: Twenty participants were included. Of these, 11 participants (55%) were female. The median age, body weight, and bleeding volume were 52 years, 62.1 kg, and 11 158 mL, respectively. The intraoperative clearance of ampicillin was 80.28 mL/min, and sulbactam was 77.23 mL/min. The fT > MIC for both ampicillin and sulbactam tended to be lower with bleeding > 20 000 mL than with less bleeding. Plasma concentrations of ampicillin and sulbactam were maintained during surgery without redosing, even after bleeding exceeded 1500 mL.

Conclusions: Even with excessive bleeding, administering 3 g of ampicillin/sulbactam every 3 h maintained sufficient plasma concentration. Redosing may be unnecessary unless total bleeding exceeds 20 000 mL.

Objectives: The objective of this study was to determine the pharmacokinetic/pharmacodynamic parameters of teicoplanin associated with optimal outcomes in glycopeptide-susceptible Enterococcus faecium (GSEF) bacteraemia.

Patients and methods: We conducted a retrospective review of GSEF bacteraemia cases treated with teicoplanin between 1 April 2009 and 30 May 2023. Total area under the concentration-time curve over 24 h (AUC₂₄) was calculated using a Bayesian approach. The free AUC₂₄ (fAUC₂₄) was estimated based on patient serum albumin levels. MICs were determined using the gradient diffusion method (Etest), and the fAUC₂₄/MIC_Etest ratio was calculated. The primary outcome was treatment failure, defined as a composite of (i) 30-day all-cause mortality and (ii) microbiological failure, defined as persistent bacteraemia (a positive follow-up blood culture obtained >72 h after initiation of appropriate therapy). Classification and regression tree analysis (CART) was employed to identify the optimal teicoplanin fAUC₂₄/MIC_Etest value associated with treatment failure.

Results: A total of 76 patients were included. Treatment failure occurred in 18 patients (23.7%). A CART-derived teicoplanin fAUC₂₄/MIC_Etest ≥ 462 was significantly associated with reduced treatment failure (P = 0.002). Multivariable regression analysis revealed that achievement of an fAUC₂₄/MIC_Etest ≥ 462 was an independent predictor significantly associated with reduced treatment failure (OR, 0.099; 95% CI, 0.005-0.562; P = 0.032).

Conclusions: An fAUC₂₄/MIC_Etest ≥ 462 was associated with a reduction in treatment failure in GSEF bacteraemia. Further studies are necessary to establish optimal pharmacokinetic/pharmacodynamic targets for GSEF bacteraemia.

[This corrects the article DOI: 10.1093/jacamr/dlaf078.].